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PURPOSE To examine the corneal transplant failure rates and associations with uveitic eye disease. METHODS The retrospective chart review identified 70 eyes from 42 patients with uveitis that underwent 40 primary transplants and 30 repeat transplants at 2 major academic centers over a 9-year period. The graft failure rate was calculated. Variables hypothesized to be associated with graft failure were analyzed as covariates using a Cox proportional hazards analysis clustered by the patients to determine their association with failure rates. RESULTS Of the 70 grafts, the mean duration of follow-up for patients was 40.6 months (range 4-90 months) and the median survival time was 24.1 months (interquartile range of 9-290 months). Twenty-two patients (52%) had graft failure. There was a higher rate of graft failure in patients with infectious uveitis as compared to those with noninfectious uveitis (hazard ratio 2.46, P = 0.031). Patients with successful grafts had their inflammation controlled for a longer period of time before transplantation as compared to those with failed grafts (38.6 vs. 13.6 months, P = 0.004). Worse preoperative visual acuities were significantly associated with graft failure (P < 0.001). CONCLUSIONS There is limited knowledge of corneal transplant outcomes in uveitic patients in the current literature. In our study, over half of the grafts failed. Infectious uveitis (especially viral) was a strong predictor of graft failure. A shorter period of inflammation control before transplantation, previously failed grafts, and worse preoperative visual acuity were also associated with graft failure.

Purpose To report the case of a ten-year old girl with torpedo maculopathy with a complete vitelliform lesion and describe associated optical coherence tomography (OCT), OCT angiography (OCTA), multifocal electroretinogram (ERG) and adaptive optics ophthalmoscopy (AOO) imaging of the lesion. Observations An asymptomatic ten-year old girl with visual acuity of 20/15 OU was referred for evaluation of possible Best's disease of her left eye. The unilaterality, location, and shape of the lesion was consistent with torpedo maculopathy. OCT and autofluorescence (AF) revealed that the entire lesion was composed of subretinal hyperreflective material that was hyperautofluorescent, consistent with vitelliform material. Within the boundary of the lesion, OCTA showed reduced choriocapillaris density while adjacent to the lesion, the choriocapillaris density was slightly increased. Microperimetry demonstrated normal sensitivity in both eyes, electrooculograms (EOG) were normal and multifocal ERG showed symmetrical mildly supernormal amplitudes. Additionally, AOO demonstrated that nasal to the lesion there were clusters of hyper-reflective areas, and immediately adjacent to the lesion cones were poorly resolved. However, there was a return to more normal photoreceptor architecture outside of the lesion. Conclusions and Importance Torpedo maculopathy lesions typically present with outer retinal attenuation and retinal pigmented epithelium (RPE) atrophy. Vitelliform material was recently observed for the first time in association with Torpedo maculopathy in a case report that described small vitelliform material at the periphery of the lesion. We report the second case of torpedo maculopathy associated with a vitelliform lesion and the first description of a torpedo lesion composed fully of presumed vitelliform material. We also describe findings of OCTA, multifocal ERG and AOO imaging in torpedo maculopathy with vitelliform lesion.

PURPOSE Stickler syndrome is associated with open-angle glaucoma, but no reports exist of adults presenting with acute angle closure. Here, we report the clinical associations and short-term outcomes in 2 patients with Stickler syndrome who presented with acute angle closure at a single tertiary referral center. OBSERVATIONS A 36-year-old female with Stickler syndrome presented with acute onset of red and painful left eye with cloudy vision. Initial intraocular pressure (IOP) was measured to be 54 mm Hg. Gonioscopy revealed no angle structures or peripheral anterior synechiae in the left eye. Two laser peripheral iridotomies were created 5 days apart without adequate IOP lowering. Left eye cataract extraction with intraocular lens implantation and Ahmed glaucoma drainage device implantation were performed with resolution of ocular hypertension.A 35-year-old male with Stickler syndrome presented with intermittent right eye pain and blurry vision. IOP was 42 mm Hg and gonioscopy revealed 270 degrees of angle closure in the right eye. The patient underwent laser peripheral iridotomy in the right eye with resolution of ocular hypertension by the next day. CONCLUSIONS Recognizing angle closure as a potential feature of Stickler syndrome can help providers adequately screen and manage patients with Stickler syndrome presenting with acutely elevated IOP.

AIM: To elucidate the association of treatment modality to vitreoretinal fibrosis and traction retinal detachment (TRD) in Coats’ disease. METHODS: A PubMed search for Coats’ disease with included studies describing eyes with clinical features and treatment course of Coats’ disease. Binary logistic regression with fibrosis at presentation and treatment type as independent variables was performed to determine predictors of TRD historically (since 1921) and in the anti-vascular endothelial growth factor (VEGF) era (since 2007). Odds ratios (OR) with 95% confidence intervals (CI) reported. RESULTS: Of 175 articles described 1183 eyes. Vitreoretinal fibrosis increased from presentation (5.4%) to follow-up (15.5%) and TRD increased from 0.44% to 3.9% at follow up. Laser was protective against vitreoretinal fibrosis (OR 0.6, 95%CI 0.4-0.9) but TRD was borderline (OR 0.6, 95%CI 0.3-1.1). Cryotherapy showed a higher association with TRD (OR 1.9, 95%CI 1.0-3.7) than with vitreoretinal fibrosis (OR 0.8, 95%CI 0.5-1.2). Similarly, intravitreal anti-VEGF alone was not associated with fibrosis (OR 1.1, 95%CI 0.6-1.8) nor TRD (OR 1.1, 95%CI 0.5-2.6) but the combination of laser and anti-VEGF therapy was protective [Fibrosis: 0.1 (0.03, 0.35); TRD: 0.05 (0.01, 0.23)] compared to anti-VEGF plus cryotherapy (P

A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings.

Purpose To optimize phacoemulsification efficiency by varying the intraocular pressure (IOP) using the Centurion Vision System, a monitored forced-infusion system. Setting John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, USA. Design Laboratory investigation. Methods Porcine lenses were soaked in formalin and divided into 2.0 mm cubes; 0.9 mm balanced tips were used. Intraocular pressure levels were tested from 30 to 110 mm Hg at 10 mm Hg intervals. Vacuum was set at 500 mm Hg, aspiration at 35 mL/min, and torsional power at 60%. Efficiency (time to lens removal) and chatter (number of lens fragment repulsions from the tip) were measured. Results There was a linear relationship between efficiency and IOP. Increasing IOP led to an increase in efficiency (ie, to a decrease in time necessary to remove the lens fragment) (R2 = .5769, P = .0176). Chatter correlated with IOP in the range of 30 to 50 mm Hg (R2 = .4506, P = .0448) and was minimal at higher IOPs. Conclusions Increasing IOP in the monitored forced-infusion system improved efficiency. Chatter was also decreased or eliminated with increasing IOP. Additional studies will be required to understand the reasons for these findings. Financial Disclosure None of the authors has a financial or proprietary interest in any material or method mentioned.

To assess whether Tie2-mediated vascular stabilization ameliorates neovascular age-related macular degeneration (AMD), we investigated the impact of adeno-associated virus-mediated gene therapy with cartilage oligomeric matrix protein angiopoietin-1 (AAV2.COMP-Ang1) on choroidal neovascularization (CNV), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor (HIF) in a mouse model of the disease. We treated mice with subretinal injections of AAV2.COMP-Ang1 or control (AAV2.AcGFP, AAV2.LacZ, and phosphate-buffered saline). Subretinal AAV2 localization and plasmid protein expression was verified in the retinal pigment epithelium (RPE)/choroid of mice treated with all AAV2 constructs. Laser-assisted simulation of neovascular AMD was performed and followed by quantification of HIF, VEGF, and CNV in each experimental group. We found that AAV2.COMP-Ang1 was associated with a significant reduction in VEGF levels (29–33%, p < 0.01) and CNV volume (60–70%, p < 0.01), without a concomitant decrease in HIF1-α, compared to all controls. We concluded that a) AAV2 is a viable vector for delivering COMP-Ang1 to subretinal tissues, b) subretinal COMP-Ang1 holds promise as a prospective treatment for neovascular AMD, and c) although VEGF suppression in the RPE/choroid may be one mechanism by which AAV2.COMP-Ang1 reduces CNV, this therapeutic effect may be hypoxia-independent. Taken together, these findings suggest that AAV2.COMP-Ang1 has potential to serve as an alternative or complementary option to anti-VEGF agents for the long-term amelioration of neovascular AMD.

Purpose To compare the relative efficiency and chatter of the 30-degree 0.9 mm Kelman tip (standard tip) and Ozil Intrepid Balanced tip (torsional tip) with identical optimum settings. Setting John A. Moran Eye Center Laboratories, University of Utah, Salt Lake City, Utah, USA. Design Experimental study. Methods Porcine nuclei were fixed in formalin and cut into 2.0 mm cubes. Lens cubes were phacoemulsified with standard and torsional tips at 60% and 100% torsional amplitude with 0%, 25%, 50%, 75%, and 100% longitudinal power with monitored forced infusion. Experiments were performed at a constant vacuum, aspiration rate, and intraocular pressure. Results Linear regression showed increased efficiency with up to 75% longitudinal power at 60% torsional amplitude for both tips ( P = .046 standard; P = .0093 torsional). Longitudinal did not significantly increase efficiency at 100% torsional power for either tip. Torsional tips were on average 29% more efficient than standard tips throughout the range tested ( P P = .0028). Chatter was minimal except at 100% longitudinal power, which was greater than at 75% longitudinal power ( P P P = .0022). Conclusions Increasing up to 75% longitudinal power increased the efficiency at 60% torsional for standard and torsional tips. Torsional tips were more efficient than standard tips. Chatter was generally minimal. Torsional tips showed more chatter than standard tips at 100% longitudinal power. Financial Disclosure None of the authors has a financial or proprietary interest in any material or method mentioned.

Angiogenesis plays a key role in tumor growth. Vascular endothelial growth factor (VEGF) is a pro-angiogenic that is involved in tumor angiogenesis. When VEGF binds to membrane-bound vascular endothelial growth factor receptor 2 (mVEGFR2), it promotes angiogenesis. Through alternative polyadenylation, VEGFR2 is also expressed in a soluble form (sVEGFR2). sVEGFR2 sequesters VEGF and is therefore anti-angiogenic. The aim of this study was to show that treatment with a previously developed and reported antisense morpholino oligomer that shifts expression from mVEGFR2 to sVEGFR2 would lead to reduced tumor vascularization and growth in a murine colon cancer xenograft model. Xenografts were generated by implanting human HCT-116 colon cancer cells into the flanks of NMRI nu/nu mice. Treatment with the therapeutic morpholino reduced both tumor growth and tumor vascularization. Because the HCT-116 cells used for the experiments did not express VEGFR2 and because the treatment morpholino targeted mouse rather than human VEGFR2, it is likely that treatment morpholino was acting on the mouse endothelial cells rather than directly on the tumor cells.

We report the case of a 15-month-old boy with retinoblastoma who developed exotropia secondary to a right medial rectus infarct after intra-arterial chemotherapy. He had unilateral sporadic group C tumor (International Classification of Retinoblastoma) and was treated with intra-arterial melphalan. One week after the first session of intra-ophthalmic arterial melphalan chemotherapy, he was noted to have orbital congestion, exotropia, and right adduction limitation. Magnetic resonance imaging was suggestive of a right medial rectus infarct. The tumor showed a good response to intra-arterial chemotherapy but the exotropia persisted.

Purpose The aim of this report was to demonstrate a case of Coats disease in a patient with concurrent anisometropic amblyopia. Observations A 10-year-old boy was diagnosed with Coats disease during routine ophthalmic examination. Visual acuity was 20/20 OD and 20/50 OS with cycloplegic refraction of +1.25 (OD) and +3.25 (OS). Examination under anesthesia showed macular exudates in the left eye that encroached near the fovea superotemporally. Despite the poor visual acuity and macular exudates, the foveal architecture of both eyes appeared normal on spectral domain optical coherence tomography. Because of the differing refractive error between the two eyes in the presence of foveal-sparing exudates, anisometropic amblyopia was suspected. After initial laser therapy, the patient was started on a daily patching regimen of the right eye. The patient's vision steadily improved to 20/25 OS with a final cycloplegic refraction of +1.00 (OD), +3.00 (OS) at 2 years. This report demonstrates the importance of assessing for other common and treatable causes of vision loss in the setting of Coats disease. Conclusions and importance This case demonstrates the importance of detecting and correcting for concurrent amblyopia in pediatric retina conditions that may, on fundus examination alone, appear to have a retinal cause for reduced visual acuity.